Despite the large numbers of effective antibiotics in use today, patients are increasingly developing infections caused by multidrug-resistant (MDR) pathogens. The emergence of resistance is particularly acute in a clinical setting because of the heavy use of antibiotics. As a consequence of the widespread use of antibiotics, there currently are few if any compounds in clinical use against which resistance has not developed.
The ever increasing emergence of many relevant pathogenic strains of bacteria resistant to commonly used antibiotics is a rapidly growing concern in public health. Patients with weakened immunity because of chemotherapy, AIDS or organ transplantation or patients undergoing acute care in hospitals are significantly at risk for acquiring opportunistic bacterial infections. Strategies to find novel antimicrobial (antibacterial) compounds using bacterial genomics approaches have as yet proven largely unsuccessful.
Seven leading groups of pathogens account for the increased risk for such infections, including Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecium, streptococci, and coagulase-negative staphylococci. Resistance against commonly used classical antibiotics has emerged in all of these pathogens.
Given the increasing rate at which infectious organisms develop resistance to antibiotics currently in use, there is an urgent need to develop novel classes of potent antibiotics against molecular targets, such as lipid II. Lipid II is an ideal target for antibiotics because it is an essential component in bacterial cell wall synthesis. Biosynthesis of the bacterial membrane is a classical target for antibiotic development. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. No synthetic compounds that interfere with Lipid II have yet been developed.